Granulocytes

Granulocytes are a category of white blood cells involved in the defence against bacteria and parasites. They characterized by the presence of granules in their cytoplasm that contain, e.g., defensins, lysozymes and histamines. Granulocytes are produced via granulopoiesis in the bone marrow, and the most abundant of the granulocytes is the neutrophil granulocyte, while the other types (eosinophils, basophils, and mast cells) have lower numbers.

In the Immune cell section we have 1019 cell lineage enriched genes and 54 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 658 genes are cell lineage group enriched and an additional 15 genes are enhanced in this cell lineage. Altogether, 1692 genes are elevated and among these 136 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

Figure 1. The distribution of all genes across the five specificity categories based on transcript abundance in granulocyte cell lineage as well as in the other 5 cell lineages.

Table 1. Number of genes in the subdivided categories of elevated expression in granulocyte cell lineage.

Distribution in the six cell lineages
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Lineage enriched 4380315266 1019
Group enriched 00454204 658
Lineage enhanced 11031 15
Total 4490772471 1692

Table 2. The genes with the highest level of enriched expression in granulocyte cell lineage. "nTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of granulocyte cell lineage expression to the second highest cell lineage.

Gene Description Cell lineage distribution nTPM Specificity score
CPA3 carboxypeptidase A3 Detected in single 1115.4 5518
MS4A3 membrane spanning 4-domains A3 Detected in single 2686.3 4507
PI3 peptidase inhibitor 3 Detected in single 1763.3 4377
GATA2 GATA binding protein 2 Detected in single 513.2 4344
CLC Charcot-Leyden crystal galectin Detected in all 28756.2 2254
HDC histidine decarboxylase Detected in single 686.2 2140
GATA1 GATA binding protein 1 Detected in single 471.7 1877
TCN1 transcobalamin 1 Detected in many 2374.2 1592
RHEX regulator of hemoglobinization and erythroid cell expansion Detected in single 1312.1 1544
MS4A2 membrane spanning 4-domains A2 Detected in single 275.5 1467
CA4 carbonic anhydrase 4 Detected in single 99.5 995
TPSAB1 tryptase alpha/beta 1 Detected in single 89.3 893

Basophils

Basophils are responsible for inflammatory reactions during immune response. They have granules containing histamine, heparin, chondroitin sulfate, peroxidase and platelet-activating factor, and upon an infection they will travel from the bone marrow to the site of infection and release the granule content which will contribute to inflammation.

In the Immune cell section we have 262 basophil enriched genes and 6 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 287 genes are cell type group enriched and an additional 414 genes are enhanced in this cell type. Altogether, 963 genes are elevated and among these 50 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

Isolation of the basophils was done from whole blood. Erythrocytes were eliminated by HetaSep sedimentation method. Remaining erythrocytes, debris and cell aggregates were eliminated by gating on CD45+ cells and based on scatter profiles. The basophils were sorted as CD123+/CD193+/CD38+/CD3neg/CD11cneg/ CD15neg/CD16neg/CD20neg/CD56neg/HLA-Drneg/SSClow cells, and 2,000 – 5,800 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 44% (n=8880) of all human proteins (n=20090) are expressed in the basophils and 287 of these genes show an elevated expression in basophils compared to the other 17 cell types (see figure below).

Figure 2. The distribution of all genes across the five specificity categories based on transcript abundance in basophil cell type as well as in the other 17 cell types.

Table 3. Number of genes in the subdivided categories of elevated expression in basophils.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Immune cell enriched 137485918 262
Group enriched 011611358 287
Immune cell enhanced 8610113592 414
Total 223265307168 963

Table 4. The genes with the highest level of enriched expression in basophils. "nTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of basophil cell type expression to the second highest cell type.

Gene Description Cell type distribution nTPM Specificity score
HDC histidine decarboxylase Detected in single 686.2 2140
CPA3 carboxypeptidase A3 Detected in single 1115.4 1534
MS4A3 membrane spanning 4-domains A3 Detected in some 2686.3 1478
MS4A2 membrane spanning 4-domains A2 Detected in single 275.5 908
TPSAB1 tryptase alpha/beta 1 Detected in single 89.3 893
IL4 interleukin 4 Detected in single 474.9 861
GCSAML germinal center associated signaling and motility like Detected in single 227.7 661
TEX101 testis expressed 101 Detected in single 55.7 557
SLC45A3 solute carrier family 45 member 3 Detected in single 40.5 382
CD200R1L CD200 receptor 1 like Detected in single 85.0 379
TRIM64B tripartite motif containing 64B Detected in single 33.2 332
GATA2 GATA binding protein 2 Detected in some 513.2 330

Eosinophils

Eosinophils mainly function in defence against multicellular parasites, but they also function as antigen-presenting cells and can participate in phagocytosis. They fight parasites by releasing the toxic chemical mediators, including eosinophil peroxidase, lipase, major basic protein, RNase and DNase, contained in their granules.

In the Immune cell section we have 75 eosinophil enriched genes and 3 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 291 genes are cell type group enriched and an additional 211 genes are enhanced in this cell type. Altogether, 577 genes are elevated and among these 58 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The eosinophils were isolated from whole blood. Erythrocytes were eliminated by the HetaSep sedimentation method. Remaining erythrocytes, debris and cell aggregates were eliminated by gating on CD45+ events and based on scatter profile. The eosinophils were sorted as CD193+/CD15low/CD16low/HLA-Drlow/SSChigh cells and 8,000 – 30,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing.The transcriptome analysis shows that 43% (n=8734) of all human proteins (n=20090) are expressed in the eosinophils and 291 of these genes show an elevated expression in eosinophils compared to the other 17 cell types (see figure below).

Figure 3. The distribution of all genes across the five specificity categories based on transcript abundance in eosinophil cell type as well as in the other 17 cell types.

Table 5. Number of genes in the subdivided categories of elevated expression in esinophils.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Immune cell enriched 3115236 75
Group enriched 09313464 291
Immune cell enhanced 22598446 211
Total 53167241116 577

Table 6. The genes with the highest level of enriched expression in esinophils. "nTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of eosinophil expression to the second highest cell type.

Gene Description Cell type distribution nTPM Specificity score
SEMG1 semenogelin 1 Detected in single 26.8 239
CEBPE CCAAT enhancer binding protein epsilon Detected in many 750.4 218
ALOX15 arachidonate 15-lipoxygenase Detected in some 602.9 193
CCL23 C-C motif chemokine ligand 23 Detected in some 183.7 163
PRSS41 serine protease 41 Detected in single 10.5 105
LRRC17 leucine rich repeat containing 17 Detected in single 9.9 94
PRSS33 serine protease 33 Detected in some 1296.1 65
THBS4 thrombospondin 4 Detected in single 4.5 46
TMIGD3 transmembrane and immunoglobulin domain containing 3 Detected in some 62.8 44
ADORA3 adenosine A3 receptor Detected in many 601.6 40
SIGLEC8 sialic acid binding Ig like lectin 8 Detected in some 290.2 38
MYCT1 MYC target 1 Detected in single 30.7 33

Neutrophils

Neutrophils are considered the first line of defence in the innate immune system, and are involved in the healing of damaged tissues and the defence against infections. They are the most abundant leukocytes in the circulation and capture and destroy invading micro-organisms by phagocytosis, release of bactericidal and protein-destroying compounds from the granules, and by the generation of neutrophil extracellular traps (NETs), but they also participate as mediators of inflammation.

In the Immune cell section we have 231 neutrophil enriched genes and 25 of these genes has the highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed. In addition, 339 genes are cell type group enriched and an additional 474 genes are enhanced in this cell type. Altogether, 1044 genes are elevated and among these 108 also show highest expression in blood or lymphoid tissues when comparing all tissues and organs analysed.

The neutrophils were isolated from whole blood. Erythrocytes were eliminated by the HetaSep sedimentation method. Remaining erythrocytes, debris and cell aggregates were eliminated by gating on CD45+ events and scatter profiles. The neutrophils were sorted as CD15+/CD16+/SSChigh cells, and 50,000 – 190,000 cells were sorted per sample for transcriptomic analysis by mRNA-sequencing. The transcriptome analysis shows that 43% (n=8667) of all human proteins (n=20090) are expressed in the neutrophils and 339 of these genes show an elevated expression in neutrophils compared to the other 17 cell types (see figure below).

Figure 4. The distribution of all genes across the five specificity categories based on transcript abundance in neutrophil cell type as well as in the other 17 cell types.

Table 7. Number of genes in the subdivided categories of elevated expression in neutrophils.

Distribution in the 18 cell types
Detected in singleDetected in someDetected in manyDetected in all Total
Specificity
Immune cell enriched 77566533 231
Group enriched 011314779 339
Immune cell enhanced 6985161159 474
Total 146254373271 1044

Table 8. The genes with the highest level of enriched expression in neutrophils. "nTPM" shows the transcript level as protein-coding transcripts per million. Specificity-score corresponds to the score calculated as the fold change of neutrophil cell expression to the second highest cell type.

Gene Description Cell type distribution nTPM Specificity score
PI3 peptidase inhibitor 3 Detected in some 1763.3 1021
CHI3L1 chitinase 3 like 1 Detected in single 470.4 495
CXCL8 C-X-C motif chemokine ligand 8 Detected in some 483.0 451
ANXA3 annexin A3 Detected in single 207.7 320
TGM3 transglutaminase 3 Detected in single 30.3 295
CXCL1 C-X-C motif chemokine ligand 1 Detected in single 47.3 243
BTNL3 butyrophilin like 3 Detected in single 22.3 206
C4BPA complement component 4 binding protein alpha Detected in single 29.5 137
MMP9 matrix metallopeptidase 9 Detected in some 272.2 127
MME membrane metalloendopeptidase Detected in some 139.4 122
CXCL6 C-X-C motif chemokine ligand 6 Detected in single 10.4 104
OTX1 orthodenticle homeobox 1 Detected in single 9.4 95